Search

We report a 71-year-old man with non-B non-C chronic liver damage who had been regularly visiting our hospital since he was 38 years of age. He underwent three partial hepatectomies for hepatocellular carcinoma (HCC) diagnosed at 65, 67, and 71 years of age, respectively. A histopathological examination showed moderately-differentiated HCC, and chronic hepatitis with mild fibrosis stage in non-tumor areas. alpha-fetoprotein (AFP) and PIVKAII were not useful for the early prediction of HCC, but TERT promotor mutation (C228T) in serum cell-free DNA was useful. This is the first report on the importance of long-term follow-up in non-B non-C chronic liver damage, regardless of the fibrosis stage.

Background: The aims of this study were to evaluate the efficacy of additional treatment, especially lenvatinib-transarterial chemoembolization (TACE) sequential therapy, for unresectable hepatocellular carcinoma (HCC). Methods: Consecutive 56 patients who underwent lenvatinib treatment were reviewed. Oncological aggressiveness of tumor was estimated using a dynamic CT enhancement pattern classification, and clinical impact of subsequent treatment was investigated through analysis of progression-free survival (PFS), post-progression survival (PPS), and multivariate analysis of potential confounders for survival after progression during lenvatinib therapy. Results: Heterogeneous enhancement patterns (Type-3 and -4), which are reportedly associated with higher oncological aggressiveness of HCC, were associated with better objective response to lenvatinib compared to homogeneous enhancement pattern (Type-2) (86 and 85% vs. 53% in modified Response Evaluation Criteria in Solid Tumors), resulting in similar PFS (p = 0.313). Because of significantly worse PPS, overall survival of Type-4 tumor was poor compared to Type-2 or -3 tumors (p = 0.009). However, subgroup of patients who achieved subsequent treatment showed significantly better PPS, regardless of CT enhancement pattern. Multivariate analysis confirmed that use of lenvatinib-TACE sequential treatment after progression during lenvatinib therapy was associated with better PPS (hazard ratio [HR], 0.08; 95% CI, 0.01–0.71; p = 0.023), while Type-4 enhancement pattern was correlated with worse PPS (HR, 2.92; 95% CI, 1.06–8.05; p = 0.039). Conclusion: Oncological aggressiveness of HCC estimated by CT enhancement pattern was predictive of PPS after progression during lenvatinib. Successful subsequent treatment with lenvatinib-TACE sequential therapy may offer survival benefit regardless of CT enhancement pattern of HCC.

A 53-year-old man presented with fulminant hepatitis due to de novo hepatitis B. He had been diagnosed previously with adult T-cell leukemia (ATL) and previously resolved hepatitis B virus infection. The ATL had been treated with cord blood transplantation (CBT). He developed fulminant hepatitis 18 months after CBT, 15 months after the withdrawal of immunosuppressants, and 10 months after vitreous injections of methotrexate for ATL-related retinal infiltration. The aggressive medical protocol included entecavir, prednisolone, plasma exchange, hemodialysis, and bilirubin adsorption. We herein report successful medical treatment for fulminant de novo hepatitis B in a patient considered unsuitable for liver transplantation.

Background and Aims: This study aimed to identify the utility of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) as a predictor of the response of hepatocellular carcinoma (HCC) to lenvatinib. Methods: We evaluated 28 consecutive patients with HCC diagnosed by dynamic CT or magnetic resonance imaging combined with 18F-FDG-PET/CT. The tumor-to-normal liver standardized uptake value ratio (TLR) of the target tumor was measured before treatment using 18F-FDG-PET/CT, with a TLR ≥2 classified as a high potential for malignant HCC. The treatment response was evaluated 2 weeks after the initiation of lenvatinib using modified Response Evaluation Criteria in Solid Tumors. Results: Of the 28 patients, 12 (43%) presented with a TLR ≥2. Evaluation of the treatment response at 2 weeks in these 12 patients revealed that 2 (17%) exhibited a complete response, 8 (67%) a partial response, 2 (17%) stable disease, and none with progressive disease. Therefore, 10 of the 12 patients (83%) experienced an objective response to lenvatinib. On the other hand, 7 of the 16 patients with a TLR p = 0.028) is a useful predictor of an early objective response at 2 weeks. Conclusion: Patients with unresectable HCC showed a good early treatment response to lenvatinib. High TLR (≥2) may be a useful predictor of an extremely rapid treatment response.

We experienced two cases of hepatitis C virus (HCV) eradication failure in patients with a history of non-responsiveness to previous treatments with direct-acting antiviral agents (DAAs) who were subsequently treated with the combination of glecaprevir and pibrentasvir (GLE/PIB). Direct sequencing at commencement of GLE/PIB therapy showed non-structural protein (NS) 5A-P32 deletion in the first patient and NS5A-R30E/Q54H/A92K in the second patient (both genotype 1b). The common point was that L31/Y93 was double wild-type, and the IL28B polymorphism was non-TT type. Even when L31/Y93 is double wild-type, other NS5A mutations may affect the DAA re-treatment outcome. We analyzed the transition of amino acid mutations at NS5A by ultra-deep sequencing.

Adult-onset type II citrullinemia (CTLN2) is a urea cycle disease characterized by neurological and psychiatric abnormalities associated with hyperammonemia. One of the pathological features of CTLN2 is the presence of hepatocyte steatosis. The condition progresses in almost all CTLN2 patients to nonalcoholic fatty liver disease (NAFLD). We herein report a 74-year-old woman who developed CTLN2 without hepatocyte steatosis. The diagnosis was based on clinical and laboratory findings and confirmed by two liver biopsies conducted within 7 years, as well as by a DNA analysis, which demonstrated mutations in the SLC25A13 gene. We describe a rare CTLN2 case without hepatocyte steatosis in an elderly woman who responded well to a low-carbohydrate diet.

Background The prognostic factors of morbidity and mortality in patients with lean NAFLD (body mass index 2) are unknown. Methods In this retrospective study, 446 Japanese patients with histopathologically-confirmed NAFLD (lean NAFLD, n = 170) were followed for liver events, cardiovascular events, type 2 diabetes mellitus, and non-liver malignancies. The median observation period was 4.6 years. We also investigated the predictors of severe fibrosis (stage 3–4) and mortality in lean NAFLD patients. Results Glycolipid metabolic markers, liver function tests, NAFLD fibrosis score (NFS), and histological scoring were significantly lower in lean NAFLD patients than in non-lean NAFLD. The incidence of liver cancer was higher while that of T2DM was lower in lean NAFLD. Kaplan–Meier analysis showed no significant difference in overall survival between the lean and non-lean NAFLD. Multivariate analysis of data of lean NAFLD identified NFS ≥ − 1.455 as significant independent predictor of severe fibrosis, while history of liver cancer and NFS ≥ − 1.455 were predictors of overall survival. Conclusions Although patients with lean NAFLD have better histopathological and biochemical profile compared to patients with non-lean NAFLD, the prognosis is not different between the two groups. Lean NAFLD patients with NFS ≥ − 1.455 or history of liver cancer should be monitored carefully during follow-up.

A 53-year-old man presented with fulminant hepatitis due to de novo hepatitis B. He had been diagnosed previously with adult T-cell leukemia (ATL) and previously resolved hepatitis B virus infection. The ATL had been treated with cord blood transplantation (CBT). He developed fulminant hepatitis 18 months after CBT, 15 months after the withdrawal of immunosuppressants, and 10 months after vitreous injections of methotrexate for ATL-related retinal infiltration. The aggressive medical protocol included entecavir, prednisolone, plasma exchange, hemodialysis, and bilirubin adsorption. We herein report successful medical treatment for fulminant de novo hepatitis B in a patient considered unsuitable for liver transplantation.

Objective: The aim of this study was to evaluate the performance of pretreatment computed tomography (CT) enhancement of hepatocellular carcinoma (HCC) as a potential predictor of response to lenvatinib and its relevance to survival outcomes. Methods: We evaluated 51 consecutive patients who received lenvatinib treatment for unresectable HCC. On imaging analysis, pretreatment arterial/portal phase dynamic CT images were classified as follows: type 2, homogeneous enhancement pattern with increased arterial blood flow; type 3, heterogeneous enhancement pattern with a septum-like structure; and type 4, heterogeneous enhancement pattern with irregularly shaped ring structures. Treatment response was evaluated using modified Response Evaluation Criteria in Solid Tumors at 2–12 weeks after initiation of lenvatinib, and the correlations between the CT enhancement patterns and response to lenvatinib or survival outcomes were investigated. Results: Of the 51 patients, 38 (75%) experienced an objective response (OR). ORs were significantly more common in heterogeneously enhanced HCC (types 3 and 4) than in homogeneous HCC (type 2) (83 vs. 53%, respectively; p = 0.037). Multivariate analysis revealed that pretreatment heterogeneous enhancement pattern is an independent predictor for response to lenvatinib (odds ratio, 4.75; p = 0.042). Presence of OR was associated with longer progression-free survival (PFS) (hazard ratio, 0.36; p = 0.017), and patients with oncologically aggressive type 3 and 4 tumors showed similar PFS to those harboring type 2 tumors (p = 0.455), reflecting that OR was more common in type 3 or 4 tumors compared with type 2 tumors. Although postprogression survival was extremely poor in patients with type 4 tumors (p = 0.064), overall survival after introduction of lenvatinib was not statistically different among the three groups of patients (p = 0.053). Conclusion: The CT enhancement pattern of HCC may predict response to lenvatinib. OR seems to occur more frequently in HCC with oncologically aggressive features and may contribute to prolonged survival through a prolonged progression-free interval, even in an oncologically poor-risk group of patients.

Background: The aims of this study were to identify useful predictors of early tumor response to lenvatinib, and to evaluate the utility of estimation of tumor differentiation from pretreatment image analysis. Methods: We evaluated 37 consecutive patients with unresectable hepatocellular carcinoma (HCC) diagnosed by dynamic computed tomography (CT) who received lenvatinib. Pretreatment arterial- and portal-phase dynamic CT images were classified into three enhancement patterns: Type-2 is a homogeneous enhancement pattern with increased arterial blood flow; Type-3 is a heterogeneous enhancement pattern with a septum-like structure; and Type-4 is a heterogeneous enhancement pattern with irregularly shaped ring structures. Generally, macroscopic classification of the nodular type of SNEG and CMN types strongly relates to the Type-3 enhancement pattern, and histologically, the Type-1 enhancement pattern represents well-differentiated HCC, while the Type-2 and -3 patterns represent moderately-differentiated HCC; the Type-4 enhancement pattern is a significantly specific feature for predicting poorly-differentiated HCC. Treatment response was evaluated using mRECIST at 8–12 weeks after initiation of lenvatinib. Results: In early treatment response evaluation, 6 of 37 patients (16%) achieved a complete response (CR), 22 (59%) experienced a partial response (PR), 6 (16%) had stable disease (SD), and 3 (8%) had progressive disease (PD); therefore, 28 of 37 patients (76%) experienced an objective response (OR). By dynamic CT enhancement pattern using mRECIST, the objective response rate (ORR) was significantly elevated along with increasing heterogeneity of enhancement pattern from Type-2 (54%) to Type-4 pattern (89%; P=0.046). Multivariate logistic regression analysis revealed that a pretreatment dynamic CT heterogeneous enhancement pattern (Type-3 and -4) (hazard ratio, 6.12; P=0.040) is a useful predictor of early OR. Conclusion: Lenvatinib provided a good early treatment response in patients with unresectable HCC. Estimation of tumor differentiation using image analysis was also useful for predicting early tumor response.

The aim of this study was to clarify the utility of a no-touch pincer ablation procedure that uses bipolar electrodes to prevent intrasubsegmental tumor recurrence after radiofrequency ablation (RFA) for patients with hepatocellular carcinoma (HCC) compared to surgical resection.We evaluated 175 consecutive patients with HCC (single nodule, tumor diameter ≤ 30 mm) who underwent surgical resection (146 received partial resection) and 313 patients who received RFA; 277 patients received touch ablation using a monopolar or bipolar RFA device, and 36 received no-touch ablation using a bipolar RFA device. Pretreatment arterial and portal phase dynamic computed tomography (CT) or magnetic resonance imaging (MRI) images were classified into four enhancement patterns: Type 1 and Type 2 are homogeneous enhancement patterns without or with increased arterial blood flow, respectively; Type 3 is a heterogeneous enhancement pattern with a septum-like structure; and Type 4 is an irregularly shaped ring structure enhancement pattern.Cumulative recurrence rates significantly differed between procedures (surgical resection, 7.5%; no-touch ablation, 2.9%; and touch ablation, 17.7% at the third year; P = 0.005). Multivariate Cox proportional hazards analysis revealed that enhancement pattern type (Type 3: hazard ratio [HR], 2.95; P = 0.002; and Type 4: HR, 3.88, P = 0.002), treatment procedure (touch ablation: HR, 3.36; P 0.001), and serum α-fetoprotein level (≥30 μg/L: HR, 1.87; P = 0.009) were significant predictors of intrasubsegmental recurrence. No significant differences between no-touch ablation and surgical resection were observed.The no-touch pincer ablation procedure has the potential to prevent intrasubsegmental recurrence after RFA for patients with HCC to the same degree as partial resection.

Background Recently, the importance of quality assurance (QA) for cancer screening has gained increasing attention in Japan. This study aimed to evaluate QA process indicators for population-based colorectal cancer screening during 2003-13. Methods A national cancer screening database was used to evaluate the following process indicators: the positivity rate, diagnostic follow-up rate, unidentified results rate, non-compliance with diagnostic follow-up rate, cancer detection rate and positive predictive value (PPV). Results The positivity rate remained constant at 6.5% until 2011, and then increased slightly thereafter. During 2003-13, the cancer detection rate increased from 0.15% to 0.21%, and the PPV increased from 2.2% to 3.1%. Although the diagnostic follow-up rate increased from 58% to 67%, the non-compliance with diagnostic follow-up rate decreased from 24% to 16% and the unidentified results rate decreased from 18% to 17%. Conclusions During the study period, the QA process indicators for colorectal cancer screening in Japan generally improved. However, the recent increase in the positivity rate requires careful observation. Innovative solutions are needed to increase the diagnostic follow-up rate.